P4-10-11: Genetic and Environmental Predictors, Endogenous Hormones and Growth Factors and Risk of Estrogen Receptor-Positive Breast Cancer in Japanese Women.

Abstract

Abstract The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We have recently demonstrated that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive subtype. It is necessary to establish risk factors capable of predicting the risk of ER-positive breast cancer which will enable the efficient selection of candidates for preventive chemotherapy. We analyzed genetic factors, including 14 single nucleotide polymorphisms (SNPs), environmental risk factors (body-mass index (BMI), age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3)) and mammographic density in 913 women with breast cancer and 278 disease-free controls. To identify important risk factors, risk prediction models for ER-positive breast cancer in both pre- and postmenopausal women were created by logistic regression analysis. In premenopausal women, 1 SNP (CYP19A1-rs10046), age, pregnancy, breastfeeding, alcohol intake, serum levels of prolactin, testosterone and IGFBP3 were considered to be risk predictors. In postmenopausal women, 1 SNP (TP53-rs1042522), age, BMI, age at menopause, serum levels of testosterone and IGF1 were identified as risk predictors. Risk factors may differ between women of different menopausal status, and inclusion of common genetic variants and serum hormone measurements as well as environmental factors might improve risk assessment models. Further validation studies will clarify appropriate risk groups for preventive chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-11.